Persistent viral infection may be an important contributing cause of Alzheimer's disease, either because the amyloid-β associated with Alzheimer's disease is a part of the innate immune response, and infection thereby increases production, or because persistent infection drives the chronic inflammation that disrupts the biochemistry of brain tissue. If viral infection does drive Alzheimer's disease, it may go some way towards explaining why the disease doesn't correlate with lifestyle factors such as weight, activity, and so forth, anywhere near as well as is the case for other common age-related conditions. It all sounds plausible, and the various mechanisms that may be involved certainly exist, but the supporting evidence from patient data is so far mixed, despite a few quite compelling studies. The hypothesis is by no means concretely demonstrated, but researchers here suggest that pathology may require multiple viruses, a possible explanation for confounding data in studies that only focus on one type of viral infection.
Using a three-dimensional human tissue culture model mimicking the brain, researchers have shown that varicella zoster virus (VZV), which commonly causes chickenpox and shingles, may activate herpes simplex (HSV), another common virus, to set in motion the early stages of Alzheimer's disease. Normally HSV-1 - one of the main variants of the virus - lies dormant within the neurons of the brain, but when it is activated it leads to accumulation of tau and amyloid beta proteins, and loss of neuronal function, signature features found in patients with Alzheimer's.
Researchers re-created brain-like environments in small 6 millimeter-wide donut-shaped sponges made of silk protein and collagen. They populated the sponges with neural stem cells that grow and become functional neurons capable of passing signals to each other in a network, just as they do in the brain. Some of the stem cells also form glial cells, which are typically found in the brain and help keep the neurons alive and functioning.
The researchers found that neurons grown in the brain tissue can be infected with VZV, but that alone did not lead to the formation of the signature Alzheimer's proteins tau and beta-amyloid - the components of the tangled mess of fibers and plaques that form in Alzheimer's patients' brains - and that the neurons continued to function normally. However, if the neurons already harbored quiescent HSV-1, the exposure to VZV led to a reactivation of HSV, and a dramatic increase in tau and beta-amyloid proteins, and the neuronal signals begin to slow down. "It's a one-two punch of two viruses that are very common and usually harmless, but the lab studies suggest that if a new exposure to VZV wakes up dormant HSV-1, they could cause trouble."